Endometriosis As a Chronic Endothelial Disorder: Thromboinflammation, Vascular Reprogramming, and Systemic Cardiovascular Risk Publisher Pubmed



Zahiri Z ; Alborzi S ; Majlesi Z A ; Farahani N ; Zamanifard S ; Etezadi A ; Nikdoust F
Source: International Immunopharmacology Published:2026

Abstract

Microvascular thromboinflammation is a pervasive yet under-recognized driver of multisystem morbidity that links focal endothelial injury to distal organ dysfunction through interacting cellular and plasmatic networks. Contemporary paradigms remain fragmented: clinicians often treat symptoms or isolated pathways, trials enroll biologically heterogenous populations, and candidate biomarkers lack harmonized standards—together impeding translation from mechanistic insight to durable patient benefit. In this review we synthesize the evidence into a cohesive, systems-level architecture in which endothelial activation, platelet hyperreactivity, innate immune effectors (including NETosis), and impaired fibrinolysis form predictable feed-forward circuits that generate organ-selective vulnerability. We propose an integrated diagnostic-translational toolkit that anchors spatially resolved imaging endophenotypes (molecular PET, quantitative perfusion MRI, advanced flow imaging) to fluid-phase molecular readouts (cfDNA topology, NET fragments, platelet transcriptomes, endothelial microparticles) and multi-omic modules. This framework enables reproducible endotype discovery and supports biomarker-guided, stage-specific interventions. Translational strategies prioritized here include targeted anti-NET approaches, precision layering of antiplatelet/anticoagulant therapy, endothelial-directed redox and metabolic reprogramming, selective epigenetic modulation, and lesion-directed nanoparticle delivery; each is linked to companion biomarker and imaging readouts and tailored safety considerations—especially for reproductive-age populations. To accelerate clinical impact we recommend a coordinated roadmap: (i) rigorous causal validation across human-relevant platforms and scaled animal models; (ii) consensus preanalytic and analytic standards with reference materials for key thromboinflammatory biomarkers; (iii) prospective cohorts embedding serial imaging and liquid-biopsy multi-omics to derive and validate endotypes; and (iv) adaptive, biomarker-enriched clinical trials with organ-relevant surrogate endpoints and long-term vascular surveillance. By aligning mechanistic clarity, diagnostic fidelity, and pragmatic trial design, this integrated approach aims to convert mechanistic knowledge into precision diagnostics and therapies—and to transform microvascular thromboinflammation from an intractable clinical problem into a tractable target for prevention and repair. © 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.